New improved antibiotics are continually in demand, for the treatment of diseases in man. Antibiotic resistant organisms are continually a problem, with Vancomycin the last defense, particularly in hospitals. Especially in hospitals, isolates, which are vancomycin resistant, are becoming more common. A recent survey found 7.9% of Enterococci in United States hospitals are now vancomycin resistant. “Nosocomial Enterococci Resistant to Vancomycin” Morbidity and Mortality Weekly Report 42(30):597–598(1993). Further resistance of Vancomycin and other antibiotics to Enterococcus faecium is reported, Handwergers. et al., Clin. Infect. Dis. 1993(16),750–755. Resistance organisms are also a problem for other important antibiotics, which includes methicillin.
Clearly, antibiotic resistance is a growing public health problem and having new antibiotics available could provide additional options for physicians in treatment regimens.
The medical community recognizes that there is an ongoing need for additional antibiotics. The search for new antibiotics which exhibit antibacterial activity against vancomycin-resistant isolates and having structures which are not derivatives of vancomycin are particularly appealing.
Antibiotics described in the literature include: Xanthoquinodins, Tabata, Noriko; Suzumura, Yasuko; Tomoda, Hiroshi; Masuma, Rokuro; Haneda, Katsuji; Kishi, Masanori; Iwai, Yuzuru; Omura, Satoshi. Xanthoquinodins, new anticoccidial agents produced by Humicola sp.: production, isolation, and physico-chemical and biological properties. J. Antibiot (1993),46(5),749–55. Tabata, Noriko; Tomoda, Hiroshi; Matsuzaki, Keiichi; Omura, Satoshi. Structure and biosynthesis of xanthoquinodins, anticoccidial antibiotics. J. Am. Chem. Soc. (1993), 115(19), 8558–64. Omura, Satoshi; Koda, Hiroshi; Masuma, Rokuro; Haneda, Katsuji; Iwai, Yuzuru. Anticoccidial agents manufactured with Humicola. (1994), 25 pp., JP 06116281 A2 19940426. Tabata, Noriko; Tomoda, Hiroshi; Iwai, Yuzuru; Omura, Satoshi. Xanthoquinodin B3, a new anticoccidial agent produced by Humicola sp. FO-888. J. Antibiot. (1996), 49(3), 267–71 and Pinselic acid, related to Cyan-416 D is reported by Law, Kai-Kwong; Chan, Tze-Lock; Tam, Shang Wai; Shatin, N. T. Synthesis of pinselic acid and pinselin. J. Org. Chem. (1979), 44(24), 4452–3.
However, all of the above-disclosed antibiotics are distinct from the present invention.